| Project/Area Number |
16K10773
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Neurosurgery
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| Research Institution | Fujita Health University |
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Principal Investigator |
OHBA SHIGEO 藤田医科大学, 医学部, 准教授 (80338061)
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| Co-Investigator(Kenkyū-buntansha) |
廣瀬 雄一 藤田医科大学, 医学部, 教授 (60218849)
八幡 直樹 藤田医科大学, 医学部, 助教 (60450607)
秦 龍二 藤田医科大学, 医学部, 教授 (90258153)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | glioma / mutant IDH / iPS / グリオーマ / IDH変異 / 網羅的遺伝子解析 / 網羅的代謝解析 / 神経膠腫 / 変異型IDH / 腫瘍化 / 代謝 / IDH1 / がん代謝 |
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| Outline of Final Research Achievements |
To make mutant IDH1-induced iPS-derived glioma cells, iPS cells was transfected with the construct expressing mutant IDH1. The cells expressing high level of mutant IDH1 did not grow, whereas the cells expressing low level of mutant IDH1 maintained growth. The cells expressing low level of mutant IDH1 have been differentiating into astrocyte.
To investigate the differences between astrocyte-derived glioma cells transformed by mutant IDH1 and by H-Ras, comprehensive gene analysis, and metabolic analysis were performed using these cells. New therapeutic targets have been searched based on these data. For example, it was found that mutant IDH1 reduced protoporphyrinogen Ⅸ by increasing the activity of enzymes associated with degradation of protoporphyrinogen Ⅸ.
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| Academic Significance and Societal Importance of the Research Achievements |
神経膠腫は脳腫瘍の中でも頻度の多い腫瘍の一つであるが、既存の治療法では予後は必ずしもよくなく、その原因の一つとして分子発生学的な解明が十分になされていない点があげられる。
本研究では、変異型IDHによる脳腫瘍モデルを作成し、その性質を解明することで新規治療法の開発へつながりうる。また、変異型IDHを有する神経膠腫と有さない神経膠腫の差異を検討することで、それぞれの特質にあった治療法の開発をめざす。本研究から得られる結果は治療困難な病気の新たなる治療法へとつながりうる非常に有意義なものと考える。
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